Giving Injured Hearts a Lift

Some day it may be possible to repair hearts that have suffered a heart attack by using stem cells derived from the patient’s own skeletal muscle tissue, such as the muscles of the arms and legs. This is the belief of scientists at Children’s Hospital of Pittsburgh of UPMC, who have already shown success using human skeletal muscle cells to treat a mouse model of myocardial infarction (heart attack).

But the use of stem cells from skeletal muscle tissue is just one of numerous promising applications being explored by Johnny Huard, PhD, and his team at Children’s Stem Cell Research Center. In addition to heart repair, stem cells from muscle tissue could be used for the treatment of Duchenne muscular dystrophy (DMD), a devastating disease that affects one in every 3,500 boys. DMD is a genetic disease caused by a lack of the protein dystrophin. Dystrophin supports muscle cell structure and when absent causes a breakdown of the muscle, which results in the patient typically being confined to a wheel chair by the age of 10 and death in their early 20s. Therapies are also under investigation for the treatment of sports and military related injuries as well as treatments for osteoarthritis arthritis.

The novel muscle-derived human stem cells discovered by Dr. Huard’s team are called myoendothelial cells. They are found in the walls of blood vessels of skeletal muscle, which can be isolated from a small biopsy of the patient’s biceps, quadriceps, or other skeletal muscles.

In the study involving heart repair, Dr. Huard’s team, located in the John G. Rangos Sr. Research Center, human muscle-derived myoendothelial cells are transplanted into the hearts of mice that have experienced heart damage similar to that of people who have suffered a heart attack. The transplanted stem cells stimulated the growth of new blood vessels in the heart and reduced the formation of scar tissue at the injury site and thereby dramatically improved the function of the injured left ventricle of the heart.

“This study confirms our belief that this novel population of stem cells discovered in our laboratory holds tremendous promise for the future of regenerative medicine,” said Dr. Huard, who is also the Henry J. Mankin Professor and vice chair for Musculoskeletal Cellular Therapeutics in the Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine.

The myoendothelial cells used in this study were more effective at repairing the injured cardiac muscle and reducing scar tissue than previous approaches that have used muscle cells known as myoblasts, according to Dr. Huard. Six weeks after injection, the myoendothelial cell-injected hearts functioned 40 to 50 percent more effectively compared with hearts that had been injected with myoblasts.

“The important benefit of our approach is that as a therapy, it would be an autologous transplant,” said Dr. Huard. “This means that for a patient who suffers a heart attack, we would take a muscle biopsy from his or her muscle, isolate and purify the myoendothelial cells, and re-inject them into the injured heart muscle, thereby avoiding any risk of rejection by introducing foreign cells.”

Dr. Huard is an internationally recognized cell biologist conducting laboratory research into the therapeutic use of stem cells to treat a variety of musculoskeletal and orthopaedic-related diseases and injuries. He focuses on therapies to regenerate bone, cartilage, and peripheral nerve and to repair damaged skeletal muscle after sports and military-related injuries. Results of his team’s work on the heart study were published in the Journal of the American College of Cardiology in December of 2008.

According to Dr. Huard, clinical trials will be the next step in proving the safety and effectiveness of the therapy in humans.